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Deepthi Ananthula et al: Nature, consequences, detection and medical management of Bioterrorism

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Journal of Pharmaceutical and Scientific Innovation www.jpsionline.com Review Article

BIOTERRORISM: AN OVERVIEW OF AGENTS, NATURE, CONSEQUENCES, DETECTION AND MEDICAL MANAGEMENT Deepthi Ananthula1*, Raju Sama 2, Deepika Pamukuntla3, Sudha Adepu4 1St.Pauls College of Pharmacy, Turkayamjal (V) Ibrahimpatnam Road, Sagar Road, R.R (Dist), Andhra Pradesh, India--501505 2Clinical Research Associate, Shantha Biotechnics Limited, Hyderabad, Andhra Pradesh, India-500004. 3CMR College of Pharmacy, Secunderabad, R.R (Dist), Andhra Pradesh, India. 4Vikas College of Pharmacy, Suryapet (M), Nalgonda (Dist), Andhra Pradesh, India. *Email:[email protected] Received on: 10/03/12 Revised on: 16/04/12 Accepted on: 28/04/12

ABSTRACT Man has known that biological organisms and toxins were useful as weapons of war long before the germ theory of disease was understood. There are more than 1400 species of infectious organisms that are known to be pathogenic for humans; many additional organisms are capable of causing disease in animals or plants. The 20th century, with its major and minor wars, saw the research and development of biological weapons capable of immense destruction of life, which were used both by nations in preparation for military warfare and by individuals who engage in asymmetric warfare. The tools for specific defense against bioweapons consist of vaccines against both viruses and bacteria, and of antibiotics and drugs against bacteria. Vaccines and antimicrobials are of limited usefulness because of the large number of possible microbes that can be used for weapons, because of antimicrobial resistance to drugs and antibiotics, and because of limitations in technical feasibility for developing vaccines and antibacterials against certain of the agents. Induction of non-specific innate immunity by immunostimulatory vaccines (at one time licensed) needs to be explored for possible immunoprophylactic-therapeutic activity when administered immediately following exposure to bioweapon pathogens. The ideal solution to the bioweapons problem lies in measures to end their development and application throughout the world. Added to this is betterment of health, focused mainly on preventable diseases. This review deals with the specifics of the bioweapons, Nature and consequences of Bioterrorism, the detection methods and their control by vaccines, by therapy with antibacterials, and non-specific immunostimulants. KEY WORDS: Bioterrorism, infectious agents, immense destruction, Nature, Consequences INTRODUCTION Bioterrorism, broadly defined as the deliberate and malicious deployment of microbial agents or their toxins as weapons in a non-combat setting, represents perhaps the most overt example of human behavior impacting epidemic infectious diseases.1 The World Health Organization (WHO) defines a Bioweapon as an agent that produces its effect through multiplication within a target host and is intended for use in war to cause disease or death in human beings, animals, or plants.2 A nation-state, a state-sponsored terrorist, or an autonomous group might use a highly destructive biological weapon; such an event is both feasible and becoming more likely. The magnitude of the possible effects on civilian populations of their use or threatened use obliges governments both to seek to prevent such use and to develop preparedness and response plans as an integral part of existing national emergency plans.3 AGENTS OF BIOTERRORISM Biological weapons can be placed in one of four broad groups: bacteria, fungi, viruses, and biological toxins. The Centers for Disease Control and Prevention classifies agents that could be used in bioterrorism into three categories: category A, B or C (Table 1). 4 THE NATURE OF BIOTERRORISM The potential threat of bioterrorism presents challenges that set it apart from other forms of terrorism. Meaningful progress against this threat will depend on recognizing these differences and addressing the threat in the context of biological organisms and epidemic disease. Biological weapons are relatively inexpensive, easy to produce, conceal and transport, and can cause considerable damage without elaborate ‘weaponization’.

There are many naturally occurring pathogens that could be used as biological weapons, as well as those pathogens in government, university and industry laboratories. Furthermore, biological weapons facilities can be concealed within legitimate research laboratories or pharmaceutical sites. Attack with a biological weapon would produce an infectious disease epidemic that could sicken and kill large numbers of people, and in many cases could persist over a prolonged period of time as a result of contagion or continuing exposure. There would probably be no recognizable event or immediate casualties and no physical location where destruction and danger could be localized and directly addressed. Without an announcement or a fortuitous discovery, a biological attack would not be noticed for days or weeks until victims, now spread out in time and place from the initial exposure, began to appear in physician offices and hospital emergency rooms. The pathogens of greatest concern would probably not be common in the place of attack. Thus, populations would be more vulnerable to the disease, medical providers less familiar with appropriate diagnosis and treatment, and laboratories less equipped to do the assessments needed for recognition and response. In many scenarios, potential medical interventions would be limited, with a narrow window of opportunity for effective treatment where antibiotics or vaccines exist. There is also concern that advances in biotechnology will increasingly heighten the possibility of a novel organism bioengineered to be resistant to available antibiotics or vaccines. From the perspective of deterrence and enforcement, the distinctive characteristics of biological agents make them less susceptible to standard methods of intelligence collection or


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oversight controls. In addition, it might prove difficult or impossible to identify the perpetrators, the site of release, or even determine whether the disease outbreak was intentional or naturally occurring.5 CONSEQUENCES WHEN BIOLOGICAL WEAPONS ARE USED A spectrum of threat can be envisaged following deliberate releases (or even threats of release) of biological agents from relative insignificance to mass destruction of life or mass casualties. The scope and impact of an epidemic caused by a biological weapon would depend on the characteristics of the pathogen or toxin, the design of the weapon or delivery system, the environment in which the weapon was used, the vulnerability of the threatened population /its health status and degree of preparedness, and the speed and effectiveness of the medical and public health response. As in the case of infectious diseases, those infected experience an incubation period varying in duration from days to weeks. If sufficient numbers of people were infected by the dispersal of a biological weapon, or if the agent were contagious and person to person transmission outran disease control measures, the result could be large-scale, possibly catastrophic epidemics. The intentional or inadvertent release of infective agents that cause contagious disease, such as smallpox, may even result in a pandemic. Transmission may result from direct contact between an infected and an uninfected person. Or it may be mediated through inanimate material that has become contaminated with the agent, such as soil, blood, bedding, clothes, surgical instruments, water, food or milk. There may also be airborne or vector-borne secondary transmission. Airborne transmission can occur through coughing or sneezing, which disseminate microbial aerosol. Vector-borne transmission can occur through arthropods or other invertebrate hosts. With the exception of Variola, the other bioterrorism agents should be satisfactorily contained in hospitals through contact and droplet precautions, viz., use of hand washing, gown and simple masks. The need for airborne precautions with Variola can be recognized by the appearance of a rash, since most feel that it is not contagious until the rash appears (unlike chickenpox). Short-term: Terrorist incidents involving biological agents can cause mass casualties. This necessitates preparedness strategies aimed at the overwhelming medical resources and infrastructure requirement along with psychological support strategies combined with risk communication to face the psychological reaction of a civilian population. Long-term: The possible long-term consequences include delayed, prolonged and environmentally mediated health effects. They may manifest as chronic illness, delayed effects, new infectious diseases becoming endemic, or as effects mediated by ecological changes. Some biological agents can cause physical or mental illnesses that either remain evident or only become evident months or years later. They may extend the potential for harm of biological weapons beyond their immediate target area in time as well as space. Unanticipated long-term effects may prove more harmful than the immediate effects.

Biological agents may cause long lasting illness, e.g. Brucella melitensis and Francisella tularensis. The viral encephalitides may have permanent effects on the central and peripheral nervous system. Delayed effects include the possibilities of carcinogenesis, teratogenesis and mutagenesis. If biological agents are used to cause diseases that are not endemic in the country attacked, this may result in the disease becoming endemic, either in human populations, or in suitable vectors. The possible effects mediated by ecological change may include establishment of new foci of disease, caused by use of biological agents infective for man and animals, or the use of antiplant agents. These could exert profoundly adverse long-term effects on human health via reductions in the quality and quantity of the food supply derived from plants or animals. Psychological warfare aspects: Biological agents inspire horror and dread; they are amenable to the waging of psychological warfare. Even when not used, their mere fear can cause disruption and panic. 6 FACTORS INFLUENCING THE OUTCOME OF A POTENTIAL BIOTERRORIST ATTACK A series of factors, related both to the individual pathogen and the time and place of a potential attack were identified, summarized in Table 2.7 GLOBAL APPROACH FOR MEDICAL COUNTERMEASURES Medical and epidemiological surveillance Detection of BW agent prior inhalation is theoretically the best way to reduce casualties. Detecting devices however, are not fully efficient, in insufficient number, and cannot be permanently deployed. Efficient intelligence is needed in order to implement a defence against biological threat. The first indication of a biological attack in an unprotected population is the emergence of a rare or unexpected disease and/or the observation of a dramatic increasing number of cases. In front of a hypothetical B attack, the main challenge is to identify the first case of the disease, and to detect the concomitant or secondary cases (i.e. epidemiological approach). The epidemiological aspect of detection needs medical intelligence (before the attack) and epidemiological surveillance (before and after the attack). Medical intelligence collects data about potential risks and threats and abilities of terrorist organisations, or rogue states, to develop and use B agents. Epidemiological surveillance may be defined as the ongoing systematic collection, analysis, and interpretation of outcome-specific data for use in the planning, implementation and evaluation of public health practice.8 It can be used to point an unexpected event occurring in a population, to detect an abnormal increase of cases and to identify exposed persons. It can also retrospectively compare patients (victims) and controls in order to identify a putative exposition linked with the disease occurrence. When medical intelligence is not available or accurate, epidemiological surveillance is, and remains, the corner stone for alert and detection of a bioterrorism attack. Organisation of laboratories for rapid diagnosis and methods of detection The biological diagnosis is based on microbiologic and serological investigations. Early diagnosis requires a high index


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of suspicion following the first clinical symptoms in absence of warning systems. Microbiologic studies are important to recommend or to adapt earlier treatments. Identification and characterization of pathogens could request non-routinely disposable techniques. Unusual samples from different origin might be analysed in safety conditions. All these reasons justify a specialized laboratory network including environmental, veterinarian and hospital laboratories as well as highest biological safety level (BSL), research laboratories (BSL 3 and BSL 4) and national or World Health Organisation (WHO) reference laboratories. Detection of Bioterrorism Agents The Molecular Basis of Detection It is easy for the bioterrorist to manipulate the microscopic world for his benefits. However, it is equally easy for the biotechnologist to detect the organism and institute appropriate actions. There are still some challenges which are unique to bioterrorism and others are common for all testing situations. Ideally, detection platforms should be capable of rapidly detecting and confirming biothreat agents, including modified or previously uncharacterized agents, directly from complex matrix samples, with no false results. Furthermore, the instrument should be portable, user-friendly and capable of testing for multiple agents simultaneously. Such an instrument is yet unavailable. Detection assays must be sensitive and specific, capable of detecting low concentrations of target agents without interference from background materials. In general, nucleic acid-based detection systems are more sensitive than antibody-based detection systems. The polymerase chain reaction (PCR) assay can detect 10 or fewer microorganisms in a short period of time However, PCR requires a clean sample and is unable to detect protein toxins. Anticoagulants, leukocyte DNA and heme compounds in blood inhibit PCRs. Furthermore, cultures of the target organism are not available for archiving and additional tests after PCR analysis. The high sensitivity of the test can also be a major weakness because contaminating or carryover DNA can be amplified, resulting in false-positive results. This occurs because of operator error, contamination by environmental pathogens and carryover of DNA from previous reactions because of inadequately cleaned instruments. Quantitative real-time PCR (Q-PCR) combines PCR amplification with simultaneous detection of amplified products based on changes in reporter fluorescence proportional to the increase in product. The main Q-PCR format used for bioterrorist agents is specific target detection and a wide variety of primer and probe combinations are available from many companies in a multitude of configurations. Q-PCR can be utilized to detect several targets simultaneously using different reporter dyes for different targets. However, accurate characterization or identification of bacteria by Q-PCR is limited by the same bias and variations that are inherent in many nucleic acid techniques. The main concerns are biased nucleic acid extraction (e.g., efficiency of extraction or cell lysis if using whole-cell methods), degradation of nucleic acids by nucleases, probe and primer reactivity (i.e., sensitivity, specificity, accessibility and quantitation), and

inherent PCR bias (e.g., variances in polymerase, buffer and thermocycler performances). The ability to either extract the DNA or rupture the cells or spores for accessibility significantly influences the sensitivity, reproducibility and accuracy of any PCR based biothreat agent detection method. Additionally, the presence of inhibitors can interfere with target sites of the probes and primers, thereby resulting in false negatives. In spite of the limitations, PCR-based analysis can be highly specific and sensitive for the target of interest if the numbers of infected cells present are at or above the detection limits of the particular assay (typically 10 to 100 cells). Use of Q-PCR to obtain rapid quantitative estimates for biothreat agent presence is an invaluable asset. The new advances in size reduction and speed of thermocycling enable these units to be used both as portable and as laboratory-based platforms. Immunoassays have increasingly been used and developed for detection of infectious diseases. Developments in Established Methods Nucleic Acid Amplification: Some of these development efforts focus on improving the speed, portability and simplicity of PCR while maintaining the sensitivity and specificity. Additional approaches also investigate methods to detect nucleic acids from target agents of interest using isothermal amplification or directly from samples without using an amplification step. Nucleic Acid Sequence Based Amplification (NASBA) relies on the isothermal amplification of single stranded RNA for detection of target microorganisms. In this method, a primer binds to the target Ribo Nucleic Acid (RNA) sequence and a reverse transcriptase produces a cDNA strand. Amplification is done based on the standard reverse transcriptase processes. Assays have been developed and tested for several pathogenic microorganisms, including viruses, bacteria, fungi and protozoans. Data indicate that NASBA is a sensitive, specific, and rapid analysis method. The method may also be useful for detecting viable microorganisms when mRNA is used as the template. A method of identifying bacteria using ribosomal RNA (rRNA) was tested using E coli in a mix containing Bordetella bronchiseptica. After single-stranded DNA capture of rRNA from the bacteria on a self assembled monolayer, the bacteria were tagged with another single-stranded DNA probe labelled with fluorescein. An antifluorescein antibody labelled with peroxidase was then used to amplify the signal, followed by amperometric detection of peroxidase activity. The authors reported detection at approximately 103 E. coli cells with this method. Immunological Detection Methods: The standard method of immunological detection involves the binding of an antibody to an antigen. However, a substantial amount of research is being done on improving antibody sensitivity and specificity through the generation of recombinant antibodies, antibody fragments and phage probes. The conventional antibody consists of a Fab and an Fc fragment. Recent research focuses on generation of fragments of the classical antibody i.e the Fab, F(ab)2 and single-chain variable regions. This has been done to evaluate if they have any advantages in sensitivity, specificity or durability as compared to antibodies. Phage libraries have been developed to generate the most specific antibody or antibody fragment.


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The generation of antibody fragments has been used for the detection of Clostridium difficile toxin B, Brucella melitensis, vaccinia virus and botulinum toxin. Aptamers and Peptide Ligands: Aptamers are small DNA or RNA ligands that recognize a target by shape and not by sequence. RNA aptamers includes the ribozymes that can be engineered to generate a signal after target capture. DNA aptamers bind to a target after exposure to UV light. Short recombinant peptide sequences have also been tested as capture and detection elements. These peptide sequences maybe chemically synthesized. They can be used to detect entire organisms like Bacillus anthracis spores or toxins like ricin. Flow Cytometry: One example of the flow cytometer is the detector for the autonomous pathogen detection system (APDS). Colour-coded beads are conjugated to antibodies that bind to specific target agents. Each differently coded bead is labelled with a target specific antibody, thereby providing extensive multiplex capabilities. The PCR may be integrated into the system so that we can automatically perform confirmatory PCR on any sample that produces a positive immunoassay result Biochip Arrays: The microarray is a powerful tool that can detect specific sequences of oligonucleotides based upon their hybridization to a chip. A nanoscale detector comprised of porous silicon has been developed that can rapidly distinguish gram-positive and gram negative microorganisms. Microcavities in the silicon are coated with a synthetic organic receptor specific for lipid A. Binding of gram-negative bacteria produced a photoluminescence red shift. Microspheres arranged in cavities micro machined into a silicon wafer constitute another version of a biochip. The micropheres are coated with specific antibodies and the technology can be used to detect several proteins e.g. ricin.9 Medical measures and pharmaceutical means for prevention, therapeutic and Decontamination Good standard of hygiene is critical for the control of biological environment. It is the first preventive measure. The reinforcement of the biological environmental control using simple rules of hygiene is the first efficient corpus of measures to put in place in case of bioterrorism or biological warfare threat. These measures are the following: · Food and beverages control, · Individual and clothing hygiene, · Hospital and housing organisation, cleaning and waste

control, · Reinforcement of biological control of air and water supply

facilities, · Insects, arthropods and rodents control, · Reinforcement of hygiene and nursing good practices in

hospitals · Decontamination of ill or exposed peoples. The available medical means are drugs and procedures for prevention (vaccination, chemoprophylaxis, and passive immunoprophylaxis), treatment, decontamination or disinfection. Vaccination

Concerning vaccinations against biological warfare agents, including bioterrorism threat, the systematic vaccinations do not appear as the best solution in absence of a direct threat clearly identified. Each situation must be evaluated in a cost/benefit balance. Storage of available vaccines to face these threats seems to be justified. The best vaccines are those with a quick and high-level protective efficacy and a therapeutic ability. Procedures for use in case of emergence are identical for military and civilian populations. They must be clearly established by the health authorities. Today very few number of efficacy vaccines are available. Though vaccines may have great potential for disease prevention, they are of little or no use as therapeutics. Table 3 lists the vaccines that have been developed and licensed against Bioweapons for routine distribution.10 Passive immunoprophylaxis Passive immunisation, through the administration of specific antibodies (antibody based therapy), may provide medical protection against the main biological warfare (BW) agents. Antibodies are highly versatile defence molecules and can be produced against any foreign molecule. They can directly neutralise the pathogen (inhibition of binding to a target receptor) and/or invoke its destruction by other effectors of the immune system. As antimicrobial chemotherapy, the antibody-based therapy is immediately active and confers a rapid protection. This is especially important in the context of a bioterrorism threat where: (i) the preventive vaccination of large populations would be difficult, and (ii) vaccination procedures would be of little use during a bioterrorism crisis because immunization needs several weeks-to-months delays for protection. Antibody-based therapy may be used in pre-exposure or post-exposure prophylaxis as well as in curative therapy. It could be useful when chemotherapy is not available or insufficient, such as for toxins, some viruses, and antibiotics-resistant bacterial strains.11 Drugs for treatment Drugs usually used for treatment such as antibiotics can be useful for prophylaxis. Antibioprophylaxis could be occasionally justified in case of specified threat like bioterrorism threat or biological warfare threat. Antibiotics (fluoroquinolone antibiotics, or doxycycline) were stockpiled for this purpose. Some antiviral drugs as Ribavirin could be also recommended. In first line-prophylactic treatment, these drugs are administered in probabilistic manner. Procedures for the treatment of the most frequent biological agents have been published. They are available for anthrax, plague, tularaemia, brucellosis, haemorrhagic fevers, smallpox and botulism. (Table.4).12 Decontamination and disinfection procedures The aim of decontamination of humans is to eliminate or reduce the number of microorganisms on the surface of the body. It also protects against a secondary contamination due to the re-aerosolisation of the agents. For example the deposit of B. anthracis spores after a single exposure to an aerosol of 1, 25,000 particules/m3 is estimated to only 120 particles. Clothe removal, hand washing, a single shower with soft shampoo, water, and soap is able to eliminate 99.99% of these bacteria. In


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case of direct cutaneous exposition, the contaminated zone can be washed with a 0.5% chlorine solution (time of contact 5 min). The eyes must be rinsed with a physiological solution. Disinfection of surfaces can be performed with an active chlorine solution (3 or 5%) or with formaldehyde. Hydrogen peroxide and glutaraldehyde can be also used, but only for re-usable medical materials. The US experience demonstrates that the procedures used for decontamination were simply able to decrease the level of contamination. In certain buildings three successive sequences of decontamination have been used before the negativation of the environmental samples. The decontamination of the air-conditioning circuits is at this time extremely difficult and there is no really satisfactory procedure currently available. Medical management of victims: restriction of movement and housing of victims and exposed people in hospital or dedicated sites Quarantine and restriction of movement are critical parts of this question. Housing strategy in hospital or in dedicated sites is largely depending of the threat. Two situations can be encountered: Military operations Capability, logistic of health support and doctrine must be appreciated and adapted to face the threat and preserve the military capabilities. Mobile hospitals and dedicated non-permanent home might be equipped to maintain the best level of hygiene. All professionals would be trained to face a biological attack in poor medical conditions. The preferable sites for the implementation of these housing structures are located in the immediate vicinity of the contaminated area. The precise location is largely dependent of the wind, the climate and the local geography. National security preparedness A hospital network must be organised in the governmental security plans. This network might be able to take care of victims and exposed people. In case of bioterrorism action involving a large number of victims or exposed people, quarantine and restriction of movement would be surely a huge problem implying a political decision. Apart from the potential simultaneous number of victims (particularly in case of contagious diseases), the implementation of measures doesn’t differ from those usually used for the natural infectious diseases. Critical point will be the management of people to avoid panic and disorganisation. As armed forces, civilian security an emergency teams must be trained. This hospital network must be clearly identified by professionals and equipped with a minimum of means for housing peoples during a limited period. Drug, vaccine and other mean storage might be sized and managed to be less costly. Mobile and easily operable decontamination and disinfection facilities might be disposable. Military hospitals and are participating to the governmental security plant and have for mission to reinforce the civilian organisation but not to replace it. Training courses of experts and responsible, public information The training of professionals is fundamental for the credibility of the security plans and for the improvement of their performances. This training must be focused on the knowledge

of threats and hazards the use practice of security equipments and the implementation of procedures. Information and communication strategy of authorities is critical in these circumstances to avoid panic and disorganisation. Research and development: priorities for the next future In order to face present and future hazards, a research and development strategy combining fundamental researches and applied development in microbiology and biotechnology must be implemented. The projects combining both applied and fundamental approaches and linking different complementary research groups should be treated as a priority. There is however an important need of support for national and international research programmes on medical defence against bioterrorism. Instrumentation for forensic detection and analysis of bioweapons research, development and deployment and International espionage to discover and identify clandestine activities. Biodetection and espionage to discover and eliminate clandestine activities will be aided by instrumentation for rapid forensic detection and analysis of biological agents. Beyond science, there are the tools of diplomacy and negotiation, and engagement by the world community in the imposition of fairness in resolution of international disputes. CONCLUSION A short list of natural pathogens represents the main hazards. All efforts must be focused on medical countermeasure in order to prevent these diseases and to reduce the panic, source of dramatic disorganisation. Immunological domains belong to the first line among researches, not only for vaccine design but also to provide short-noticed specific countermeasures and treatments. The forthcoming hazards due to new biological agents and molecular or genomic technologies might not be underestimated.13, 14 It is a challenge in term of future concerns for both military and civilian responsible as well as for the whole society. People need to be informed, conscious and well prepared for the possibility of biological agents being released deliberately, whether as an act of war or of terrorism The public health infrastructure needs strengthening at local, state and national levels with trained personnel, updated labs and improved communication links to facilitate a coordinated and effective response. The medical community, as the front line of defence, needs to be engaged, and better trained to recognize and respond to bioterrorism-related illnesses. Countries need to strengthen their disease reporting systems with new tools, so that an early warning system can evolve. Local assets and capabilities should be surveyed, and a plan created for their swift and smooth augmentation at the time of need. Investment in public health will benefit us not just against bioterrorism, but also for improving the infrastructure of public health.


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4. Melanie Trull C, Tracey du Laney V, Mark Dibner D. Turning biodefense dollars into product. Nat Biotechnol 2007; 25: 179 – 184.

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8. Thacker SB, Berkelman RL. Public health surveillance in the United States. Epidemiol Rev 1988; 10: 164–90.

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10. Heilman C. The Jordan Report 2000. Accelerated development of vaccines. Division of Microbiology and Infectious Diseases. National Institute for Allergy and Infectious Diseases. National Institutes of Health, Bethesda, MD, 2000; 173.

11. Keller MA, Stiehm ER. Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev 2000; 13:602–14.

12. Casadevall A. Antibodies for defense against biological attack. Nature Biotech 2002; 20:114.

13. Rotz L, Khan A, Lillibridge SR, Ostroff M, Hughes MJ. Public health assessment of potential biological terrorism agents. Emerg Infect Dis 2002; 2:1–9.

14. Dennis C. The bugs of war. Nature 2001; 411:232–5.


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Table 1: Agents of bioterrorism

Category A

Category B

Category C

Category A agents: · are easily disseminated or transmitted from person to

person · result in high mortality rates and have the potential for

major public health impact · possess the potential to cause public panic and social

disruption · require special action for public health preparedness · provide the greatest risk to national safety

Category B agents: · are moderately easy to disseminate · result in moderate morbidity rates and low mortality rates · require specific enhancements of the CDC’s diagnostic capacity

and enhanced disease surveillance

Category C agents: · are organisms engineered to be biological

weapons of mass destruction · are easy to produce and disseminate · have the potential for high morbidity and

mortality rates and major health impact

The nine Category A agents are · Anthrax (Bacillus anthracis), · Botulism (Clostridium botulinum toxin), · Plague (Yersinia pestis), · Smallpox (Variola major), · Tularemia (Francisella tularensis), and Viral hemorrhagic fevers like · Arenaviruses. Lymphocytic choriomeningitis virus,

Junin virus, Machupo virus, Guanarito virus and Lassa fever

· Bunyaviruses. Hantaviruses, Rift Valley fever · Flaviviruses. Dengue and · Filoviruses. Ebola, Marburg

The major Category B agents and infections are · Burkholderia pseudomallei · Coxiella burnetii (Q fever) · Brucella spp. (brucellosis) · Burkholderia mallei (glanders) · Burkholderia pseudomallei (Melioidosis) · Ricin toxin (from Ricinus communis) · Epsilon toxin of Clostridium perfringens · Staphylococcus enterotoxin B · Typhus fever (Rickettsia prowazekii) · Psittacosis (Chlamydia psittaci) Food and waterborne pathogens · Bacteria. Diarrheagenic Escherichia coli, pathogenic Vibrio spp.,

Shigella spp., Salmonella spp., Listeria monocytogenes, Campylobacter jejuni and Yersinia enterocolitica

· Viruses. Caliciviruses, hepatitis A · Protozoa. Cryptosporidium parvum, Cyclospora cayatanensis,

Giardia lamblia, Entamoeba histolytica, Toxoplasma and microsporidia

Additional encephalitide viruses · West Nile, La Crosse, California encephalitis, Venezuelan equine

encephalitis, Eastern equine encephalitis, Western equine encephalitis, Japanese encephalitis and Kyasanur Forest

The major Category C agents include · Tick-borne hemorrhagic fever viruses · Crimean-Congo hemorrhagic fever virus · Tick-borne encephalitis viruses · Hantavirus · Nipah virus · Yellow fever · Multidrug-resistant tuberculosis · Influenza · Other Rickettsias · Rabies · Severe acute respiratory syndrome-

associated coronavirus (SARS-CoV)


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Table 2: Factors influencing the outcome of a potential bioterrorist attack. Factors related to the pathogen Factors related to time and place of the attack

Ease of use Geographic parameters

• Availability • Dispersion facilitation

• Ease of weaponization • Transport networks

• Ease of dispersion Targeted population

Inoculum used Healthcare facilities available

Virulence Local laboratory facilities

Mortality Local incidence of the pathogen

Person-to-person transmission Awareness

Inoculation period Definition of hierarchy

Discreet clinical picture Existence of guidelines

Ease of laboratory diagnosis • Handling of medical controversies on the disease

Availability of treatment options • Mass media interaction

Environmental and animal effects

Chronicity of the disease induced

Public perception of the pathogen

Table 3: List of vaccines that have been developed and licensed against Bioweapons

Viral Kind Bacterial Kind Yellow fever Live Multi drug resistance Tuberculosis (BCG) Live Smallpox Live Cholera Killed Japanese encephalitis Live Anthrax Killed Tick-borne encephalitis Live Plague Killed

Botulinum Antisera Coxiella burnetii (Q fever) Live


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Table 4: Treatment for Selected Bioterrorism Agents. Disease/Agent Incubation period Treatment options Chemoproprophylaxis

Anthrax (Bacillus anthracis) 1-5 days (Possibly up to 60 days).

· Ciprofloxacin; doxycycline. · Combination therapy of ciprofloxacin or doxycycline plus one or two

other antimicrobials should be considered with inhalational anthrax. · Penicillin should be considered if strain is susceptible and does not

possess inducible beta-lactamases. · If meningitis is suspected, doxycycline may be less optimal because of

poor CNS penetration. · Steroids may be considered for severe edema and for meningitis.

Ciprofloxacin or doxycycline, With or without vaccination; if strain is susceptible, penicillin or amoxicillin should be considered.

Brucellosis B. mellitensis, B. suis, B. abortus, and B. canis

5-60 days (usually 1-2 months)

· Doxycycline plus streptomycin or rifampin. · Alternative therapies: ofloxacin plus rifampin; doxycycline plus

gentamicin; Trimethoprim / Sulphamethoxazole plus gentamicin.

Doxycycline plus streptomycin or rifampin

Inhalational(pneumonic) tularemia Francisella tularensis

3-5 days (range of 1-21 days) · Streptomycin; gentamicin. · An alternative is ciprofloxacin.

Tetracycline; doxycycline; ciprofloxacin

Pneumonic plague Yersinia pestis

1-10 days (typically 2-3 days)

· Streptomycin; gentamicin. · Other alternatives include doxycycline, tetracycline, ciprofloxacin, and

chloramphenicol. · Chloramphenicol is 1st choice for meningitis except in pregnant or

lactating women.

Tetracycline; doxycycline; Ciprofloxacin

Q-Fever Coxiella burnetii 2-14 days (may be up to 40 days)

· Tetracycline; doxycycline Tetracycline; doxycycline

Smallpox(Variola major virus) 7-17 days · Supportive care. · Cidofovir shown to be effective in vitro, and in experimental animals

infected with surrogate orthopox virus.

Vaccination given within 3-4 days following exposure can prevent, or decrease the severity of, disease.

Viral Encephalitis:Venezuelan (VEE),Eastern (EEE),Western (WEE)

VEE: 2-6 days EEE, WEE: 7-14 days

· Supportive care; · analgesics, anticonvulsants as needed

None available

Viral Hemorrhagic Fevers (VHFs) Arenaviruses (Lassa, Junin, and related viruses); Bunyaviruses(Hanta,Congo-Crimean, Rift Valley); Filoviruses (Ebola, Marburg); Flaviviruses (Yellow Fever, Dengue, various Tickborne disease viruses)

4-21 days · Supportive therapy. · Ribavirin may be effective for Lassa fever, Argentine hemorrhagic

fever, and Congo-Crimean hemorrhagic fever.

Ribavarin is suggested for Congo- Crimean hemorrhagic fever and Lassa fever.

Botulinum toxin (Clostridium botulinum) 1-5 days (typically 12-36 hours)

· Supportive care – ventilation may be necessary. · Trivalent equine antitoxin (serotypes A,B,E - licensed) should be

administered immediately following clinical diagnosis. · Anaphylaxis and serum sickness are potential complications from

antitoxin. · Aminoglycosides and clindamycin must not be used.

Antitoxin might be sufficient to prevent illness following exposure but is not recommended until patient is showing symptoms.

Enterotoxin B(Staphylococcus aureus) 3-12 hours Supportive care. None available

Ricin toxin(Ricinus communis) 18-24 hours

· Supportive care. · Treatment for pulmonary edema. And Gastric decontamination if toxin

is ingested.

None available

T-2 mycotoxins (Fusarium, Myrotecium, Trichoderma, Stachybotrys and other filamentous fungi)

Minutes to hours

· Clinical support. · Soap and water washing within 4-6 hours reduces dermal toxicity;

washing within 1 hour may eliminate toxicity entirely. · No effective medications or antidotes.

None available

deepthi ananthulaet al: nature, consequences, detection ... · deepthi ananthulaet al: nature,...

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